Introduction: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

Seasonal influenza is a cause of hospitalization, especially in people with underlying disease or extreme age, and its severity may differ depending on the types and subtypes of circulating viruses. We investigated the factors associated with ICU admission or death in hospitalized patients with severe laboratory-confirmed influenza according to the viral type and subtype. An observational epidemiological study was carried out in patients aged ≥18 years from 12 Catalan hospitals between 2010 and 2016. For each reported case we collected demographic, virological and clinical characteristics. A mixed-effects logistic regression model was used to estimate crude and adjusted ORs. 1726 hospitalized patients were included: 595 (34.5%) were admitted to the ICU and 224 (13.0%) died. Lower ICU admission was associated with age ≥75 years in all influenza types and subtypes and with age 65–74 years for type A. In contrast, the 65–74 and ≥75 years age groups were associated with an increased risk of death in all types and subtypes, especially for type B (aOR 27.42, 95% CI: 4.95–151.93 and 15.96; 95% CI: 3.01–84.68). The comorbidity most closely associated with severe outcomes was immune deficiency, which was associated with death for type B (aOR 9.02, 95% CI: 3.05–26.69) and subtype A(H1N1)pdm09 (aOR 3.16, 95% CI: 1.77–5.66). Older age was a differential factor for ICU admission and death: it was associated with lower ICU admission but a risk factor for death. The comorbidity with the closest association with death was immune deficiency, mainly in influenza type B patients.

Background. In most seasons, the influenza vaccine is effective in preventing influenza, but it is not clear whether it is equally effective in preventing mild and severe cases. We designed a case-control study to compare the effectiveness of the influenza vaccine in preventing outpatient, inpatient, and severe or fatal cases of laboratory-confirmed influenza. Methods. Hospitalized patients (n = 691) with laboratory-confirmed influenza in the 2010–2011 season recruited in 29 Spanish hospitals were individually matched by age, admission/visit date, and province with an outpatient with laboratory-confirmed influenza and an outpatient control. Severe cases were considered those patients admitted to intensive care units or who died in the hospital (n = 177). We compared the influenza vaccine status of controls and outpatient cases, inpatient cases, and severe cases using conditional logistic regression adjusted for potential confounding factors. Severe and nonsevere inpatient influenza cases were compared using unconditional logistic regression. Vaccine effectiveness was (1 – odds ratio) × 100. Results. Vaccine effectiveness was 75% (adjusted odds ratio [AOR], 0.25; 95% confidence interval [CI], .16–.39) in preventing influenza outpatient cases, 60% (AOR, 0.40; 95% CI, .25–.63) in preventing influenza-associated hospitalizations, and 89% (AOR, 0.11; 95% CI, .04–.37) in preventing severe cases. In inpatients, influenza vaccination was associated with a lower risk of severe influenza (AOR, 0.42; 95% CI, .22–.80). Conclusions. Influenza vaccination prevented influenza cases and hospitalizations and was associated with a better prognosis in inpatients with influenza. The combined effect of these 2 mechanisms would explain the high effectiveness of the vaccine in preventing severe cases due to influenza.

Introduction: When influenza vaccination is ineffective in preventing influenza virus infection, it may still reduce the severity of influenza-associated disease. Here, we estimate the effect of influenza vaccination in preventing severe outcomes e.g. intensive care unit (ICU) admission and death, even though it did not prevent influenza virus infection and subsequent hospitalisation. Methods: An observational case–case epidemiological study was carried out in 12 sentinel hospitals in Catalonia (Spain) over six influenza seasons 2010/11–2015/16. Cases were individuals with severe laboratory-confirmed influenza virus infection and aged 18 years and older. For each reported case we collected demographic, virological and clinical characteristics. Logistic regression was used to estimate the crude, adjusted odd ratios (aOR) and 95% confidence intervals (CI). Results: Of 1,727 hospitalised patients included in the study, 799 were female (46.7%), 591 (34.2%) were admitted to the ICU and 223 (12.9%) died. Influenza vaccination uptake was lower in cases that required ICU admission or died (21.2% vs 29.7%, p < 0.001). The adjusted influenza vaccination effectiveness in preventing ICU admission or death was 23% (95% CI: 1 to 40). In an analysis restricted to sex, age group and antiviral treatment, influenza vaccination had a positive effect on disease severity in all age groups and categories. Conclusions: We found that influenza vaccination reduced the severity of disease even in cases where it did not prevent infection and influenza-associated hospitalisation. Therefore, increased vaccination uptake may reduce complications, ICU admission and death.

Background. Attempts to eliminate measles from a country or region may be disrupted by an imported case that affects indigenous persons. The objective of this study was to analyze epidemiological and clinical characteristics of a measles outbreak in Catalonia, Spain, in 2006. Methods. Data on cases of measles reported to the Department of Health, Generalitat of Catalonia, during the period 28 August 2006 through 8 July 2007 were collected. Suspected cases were confirmed by determination of measles-specific immunoglobulin M antibodies and/or detection of virus genome. Incidences were calculated using the estimated population of Catalonia for 2006, and 95% confidence intervals were determined assuming a Poisson distribution. The association between proportions was determined using the χ² test and Fisher's exact test. The level of statistical significance was set at a=.05. Results. A total of 381 cases were confirmed, for an incidence of 6.6 cases per 100,000 persons. A total of 89.5% of cases occurred in nonvaccinated persons, mainly those aged ≤15 months (incidence, 278.2 cases per 100,000 persons; mean age of patients, 12 months). Indigenous subjects accounted for 89.8% of cases, and laboratory confirmation of results was obtained for 87.1%. Measles genotype D4 was identified in all sequenced samples. Conclusions. The age distribution of cases of measles among children aged ×15 months suggests that the first dose of vaccine should be routinely administered at the age of 12 months.